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dc.contributor.authorHu, Chih-Chi Andrew
dc.contributor.authorDougan, Stephanie K.
dc.contributor.authorMcGehee, Annette M.
dc.contributor.authorPloegh, Hidde
dc.contributor.authorLove, John C
dc.date.accessioned2012-10-25T20:20:49Z
dc.date.available2012-10-25T20:20:49Z
dc.date.issued2009-04
dc.date.submitted2009-02
dc.identifier.issn0261-4189
dc.identifier.issn1460-2075
dc.identifier.urihttp://hdl.handle.net/1721.1/74263
dc.description.abstractXBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting that activation of XBP-1 in B cells is a differentiation-dependent event, but not the result of a UPR caused by the abundant synthesis of secreted IgM. Without XBP-1, B cells fail to signal effectively through the B-cell receptor. The signalling defects lead to aberrant expression of the plasma cell transcription factors IRF4 and Blimp-1, and altered levels of activation-induced cytidine deaminase and sphingosine-1-phosphate receptor. Using XBP-1-deficient/Blimp-1-GFP transgenic mice, we find that XBP-1-deficient B cells form antibody-secreting plasmablasts in response to initial immunization; however, these plasmablasts respond ineffectively to CXCL12. They fail to colonize the bone marrow and do not sustain antibody production. These findings define the role of XBP-1 in normal plasma cell development and have implications for management of B-cell malignancies.en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Graduate Research Fellowship Programen_US
dc.description.sponsorshipCancer Research Institute (New York, N.Y.) (Fellowship)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/emboj.2009.117en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.sourcePMCen_US
dc.titleXBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cellsen_US
dc.typeArticleen_US
dc.identifier.citationHu, Chih-Chi Andrew et al. “XBP-1 Regulates Signal Transduction, Transcription Factors and Bone Marrow Colonization in B Cells.” The EMBO Journal 28.11 (2009): 1624–1636. © 2012 European Molecular Biology Organizationen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorHu, Chih-Chi Andrew
dc.contributor.mitauthorDougan, Stephanie K.
dc.contributor.mitauthorMcGehee, Annette M.
dc.contributor.mitauthorLove, J. Christopher
dc.contributor.mitauthorPloegh, Hidde
dc.relation.journalEMBO Journalen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsHu, Chih-Chi Andrew; Dougan, Stephanie K; McGehee, Annette M; Love, J Christopher; Ploegh, Hidde Len
dc.identifier.orcidhttps://orcid.org/0000-0003-0921-3144
dc.identifier.orcidhttps://orcid.org/0000-0002-1090-6071
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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